Loss of corneodesmosin leads to severe skin barrier defect, pruritus, and atopy: unraveling the peeling skin disease.

Abstract

Generalized peeling skin disease is an autosomal-recessive ichthyosiform erythroderma characterized by lifelong patchy peeling of the skin. After genome-wide linkage analysis, we have identified a homozygous nonsense mutation in CDSN in a large consanguineous family with generalized peeling skin, pruritus, and food allergies, which leads to a complete loss of corneodesmosin. In contrast to hypotrichosis simplex, which can be associated with specific dominant CDSN mutations, peeling skin disease is characterized by a complete loss of CDSN expression. The skin phenotype is consistent with a recent murine Cdsn knockout model. Using three-dimensional human skin models, we demonstrate that lack of corneodesmosin causes an epidermal barrier defect supposed to account for the predisposition to atopic diseases, and we confirm the role of corneodesmosin as a decisive epidermal adhesion molecule. Therefore, peeling skin disease will represent a new model disorder for atopic diseases, similarly to Netherton syndrome and ichthyosis vulgaris in the recent past.

• Authors: Vinzenz Oji, Katja-Martina Eckl, Karin Aufenvenne, Marc Nätebus, Tatjana Tarinski, Katharina Ackermann, Natalia Seller, Dieter Metze, Gudrun Nürnberg, Regina Fölster-Holst, Monika Schäfer-Korting, Ingrid Hausser, Heiko Traupe, Hans Christian Hennies
• Journal: American journal of human genetics (Am J Hum Genet) Vol. 87 Issue 2 Pg. 274-81 (Aug 13 2010) ISSN: 1537-6605 [Electronic] United States
• PMID: 20691404 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CDSN protein, human
• Glycoproteins
• Intercellular Signaling Peptides and Proteins

Topics

• Base Sequence
• Child
• Chromosome Mapping
• DNA Mutational Analysis
• Epidermis (pathology)
• Family
• Glycoproteins (deficiency, genetics)
• Humans
• Intercellular Signaling Peptides and Proteins
• Male
• Models, Biological
• Molecular Sequence Data
• Pedigree
• Pruritus (complications, genetics)
• Skin (pathology, ultrastructure)